The aims of this 5-year project are to (1) initiate and complete the sequencing of the Y chromosomes of five species - rhesus macaque, marmoset, rat, bull, and opossum, and (2) complete the sequencing of the chicken W chromosome (currently ~10% sequenced). NHGRI has approved the targeting of these five Y chromosomes and the chicken W chromosome for full-scale sequencing. The new Y chromosomes will be added to our queue of three current sex chromosome sequencing projects, the mouse Y and the chicken Z and W, which are in various stages of completion. Our goal is to complete the sequence and annotation of all 8 chromosomes by the end of the next 5-year funding period. During the last 18 years, genomic studies have revealed that Y chromosomes are biologically richer and medically more important than anyone would have predicted. These genomic studies recently culminated in the finished and annotated sequences of the human and chimpanzee Y chromosomes, which are, to date, the only sex-specific chromosomes to have been sequenced from any species, vertebrate or invertebrate, plant or animal. Knowledge of the human Y chromosome sequence has allowed researchers to identify and characterize recurrent Y deletions, which have emerged as the most common of the known causes of infertility in men. Comparative sequencing in chimpanzee has shed light on the functional importance of genes on the human Y chromosome. We suspect that the sex-specific chromosomes of six of NHGRI's high-priority sequencing targets - rhesus, marmoset, rat, bull, opossum, and chicken - will also prove to be of great biomedical interest. The sequences of the new Y chromosomes will offer insight into the human Y chromosome's role in health and disease and will provide essential infrastructure for elucidating mammalian and human germ cell development and sperm production. The chicken W chromosome will be the first female-specific chromosome to be sequenced from any species. We anticipate that the sequence of the W chromosome will inform our understanding of human biology by offering insights into female fertility, oogenesis, and sex determination. PUBLIC HEALTH RELEVANCE: In recent decades, genomic studies in human, chimpanzee, and mouse have revealed that Y chromosomes are biologically richer and medically more important than anyone would have predicted. The Y chromosome sequences of five new species - rhesus macaque, marmoset, rat, bull, and opossum - will likely prove to be of great biomedical interest as well, offering insights into the human Y chromosome's role in health and disease and providing the essential infrastructure for elucidating mammalian and human germ cell development and sperm production. The chicken W chromosome, as the female counterpart of the mammalian Y, will inform our understanding of human biology by offering insights into female fertility, oogenesis, and sex determination.